Central Dogma Of Life

___________________________________________________________________________________ We know that the DNA is the carrier of genetic information in most of the living organisms. It is enclosed inside nuclear membrane and closely packed with histone. But, there are some core questions that arise from this phenomenon. That is,

How the DNA information transports from nuclear compartment to cytoplasmic compartment, and help the cell to do its function properly? And, how does DNA contribute to protein synthesis?

Large biomolecules in organism can have many functions. they can provide structure, act as catalyst for chemical reactions, serve to sense changes in their environment, provide motility and so on. DNA really does none of these things. Rather we can view it as an information storage system. The information must be decoded into proteins to allow the construction of other large molecules. The other molecules are usually proteins, another class of large polymers in the body. The DNA in genomes does not directly synthesis protein itself, but instead, uses RNA as an intermediary carrier of genetic information. When the cell needs a particular protein, the nucleotide sequence of the appropriate portion of the immensely long DNA molecule in a chromosome is first copied F IGURE 1:F LOW into RNA (a process called transcription). It is these RNA copies
of information in a cell

OF INFORMATION IN A CELL

Fig-Flow

of segments of the DNA that are used directly as templates from which, proteins are synthesized(a process called translation). The flow of genetic information in cells is therefore from DNA to RNA to protein. All cells, from bacteria to humans, express their genetic information in this way -- a principle so fundamental that it is termed the central dogma of molecular biology. The central dogma was first stated by Francis Crick in 1958.
Central dogma is represented by four stages:

1) Transcription. 4) Replication.

2) Processing of mRNA in eukaryotes. 3) Translation.

Now, the processes are discussed briefly.

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Transcription: Transcription is the process by which a molecule of DNA is

copied into a complementary strand of RNA. This is called messenger RNA (mRNA) because it acts as a messenger between DNA and the ribosomes where protein synthesis is carried out.

Splicing: In eukaryotic cell before the leave of the primary mRNA

from the nucleus it is modified in various ways during RNA processing called splicing. Intron sequences are removed from mRNA so that it contains only exon sequences. Exon sequences are known as codon sequence. Then the reformed mRNA enters into cytoplasm.

Translation: This

mature mRNA finds its way to a ribosome where it is translated. This mRNA binds with ribosomes. The mRNA is read by the ribosome as triplate codons usually beginning with an AUG, or initiator methonine codon downstream of the ribosome binding site. Complexes of initiation factors and elongation factors bring amino F IGURE 2: acylated transfer RNAs (tRNAs) into the ribosome-mRNA complex,C ENTRAL D OGMA OF L IFE matching the codon in the mRNA to the anti-codon in the tRNA, thereby adding the correct amino acid in the sequence encoding the gene. As the amino acids are linked into the growing peptide chain, they begin folding into the correct conformation. This folding continues until the nascent polypeptide chains are released from the ribosome as a mature protein.

Replication: Finally, as the final step in the Central Dogma, to transmit the

genetic information between parents and progeny, the DNA must be replicated faithfully. Replication is carried out by a complex group of proteins that unwind the superhelix, unwind the double-stranded DNA helix, and, using DNA polymerase and its associated proteins, copy or replicate the master template itself so the cycle can repeat DNA RNA protein in a new generation of cells or organisms.

Importance of central dogma in evolutionary theory

The "raw material" for evolution is mutation. Mutations are a change to the DNA sequence, which will result in an altered RNA sequence and result in a different protein. This different protein may be better, worse or the same as the original protein. If it is better and provides a reproductive advantage to the organism, it will be selected for and the mutated gene will spread within the population. The central dogma describes exactly where the raw material for evolution comes from and how that new information is created, stored and translated into actual phenotypes which can be selected for or against by the forces of evolution.

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Exceptions to the central dogma

The biggest revolution in the central dogma was the discovery of retroviruses, which transcribe RNA into DNA through the use of a special enzyme called reverse transcriptase has resulted in an exception to the central dogma; RNA DNA RNA protein. Also, some virus species are so primitive that they use only RNA proteins, having not developed DNA. With the discovery of prions, a new exception to the central dogma has been discovered, Protein Protein. That is, proteins directly replicating themselves by making conformational changes in other proteins.

Retroviruses:

Another important class of RNA virus comprises the retroviruses, so called because the genetic information flows from RNA to DNA rather than from DNA to RNA. This class includes human immunodeficiency virus 1 (HIV-1), the cause of AIDS, as well as a number of RNA viruses that produce tumors in susceptible animals. Retrovirus particles contain two copies of a single-stranded RNA molecule. On entering the cell, the RNA is copied into DNA through the action of a viral enzyme called reverse transcriptase. The resulting double-helical DNA version of the viral genome can become incorporated into the chromosomal DNA of the host and is replicated along with the normal cellular DNA.

Prions: A prion is an infectious agent composed of protein in a misfolded form which

must contain nucleic acids (either DNA, RNA, or both).Prions propagate by transmitting a misfolded protein state. When a prion enters a healthy organism, it induces existing, properly folded proteins to convert into the disease-associated, prion form; the prion acts as a template to guide the misfolding of more protein into prion form. These newly formed prions can then go on to convert more proteins themselves; this triggers a chain reaction that produces large amounts of the prion form. Although retroviruses, certain primitive viruses, and prions may violate the central dogma, they are technically not considered "alive", and thus the rule that "all cellular life follows the central dogma" still holds true.

Let's summarize:
Genes program protein synthesis via genetic messages in the form of messenger RNA. Put another way, cells are governed by a molecular chain of command: DNA RNA protein. The central dogma of molecular biology deals with the detailed residue-by-residue transfer of sequential information. It states that such information cannot be transferred from protein to either protein or nucleic acid.

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Reference: http://www.ncbi.nlm.nih.gov/books/ http://en.wikipedia.org/ http://answers.yahoo.com/ http://groups.inf.ed.ac.uk/ (School of Informatics, University of Edinburgh)

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